Evaluation of immunophenotypic and molecular biomarkers for Sézary syndrome using standard operating procedures: multicenter study of 59 cases

Abstract Differentiation between Sézary syndrome (SS) and erythrodermic inflammatory dermatoses (EID) can be challenging and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criterion. In this European multicenter study the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in SS was investigated. Peripheral blood CD4+ T-cells from 59 SS and 19 EID patients were analyzed for cell surface proteins by flow cytometry, and for copy number alterations and differential gene expression using custom made qPCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%), upregulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%) and PLS3 (66%) and downregulation of STAT4 (91%). Loss of CD26 (≥ 80% CD4+ T-cells) and/ or CD7 (≥ 40% CD4+ T-cells) and combination of altered expression of STAT4, TWIST1 and DNM3 or PLS3, could distinguish respectively 83% and 98% of SS patients from EID cases with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of SS versus EID

Diffuse Normolipemic Plane Xanthoma in a Child with Common Variable Immunodeficiency

Diffuse plane xanthoma is extremely rare in children. Although it may be associated with systemic disorders, its etiology remains obscure in a number of patients. The case of a boy with common variable immunodeficiency and normal serum lipid levels, who developed diffuse plane xanthoma during treatment with intravenous immunoglobulins, is reported

Unsachgemäße Systemtherapie bei schwerer atopischer Dermatitis – fatale Langzeitschäden

The therapeutic options for treatment of severe cases of atopic dermatitis have been limited until recently, but fundamentally improved with the approval of the first biological dupilumab at the end of 2017. With the biological tralokinumab and the Janus kinase inhibitors baricitinib and upadacitinib, further new systemic drugs have recently been approved. Nevertheless, there are cases in which modern treatment options are not taken into account, as shown by a 28-year-old patient with serious side effects from long-term treatment with systemic glucocorticoids. In addition to the extensive clarification of the consequential damage, guideline-based therapy with dupilumab was initiated as well as interdisciplinary cooperation with endocrinologists, ophthalmologists, osteologists and nutritionists

Evaluation of immunophenotypic and molecular biomarkers for Sézary syndrome using standard operating procedures: multicenter study of 59 cases

Differentiation between Sezary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sezary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sezary syndrome were investigated. Peripheral blood CD4(+) T cells from 59 patients with Sezary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sezary cells showed MYC gain (40%) and MNT loss (66%); up-regulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%), and PLS3 (66%); and down-regulation of STAT4 (91%). Loss of CD26 (>= 80% CD4(+) T cells) and/or CD7 (>= 40% CD4(+) T cells) and combination of altered expression of STAT4, TWIST1, and DNM3 or PLS3 could distinguish, respectively, 83% and 98% of patients with Sezary syndrome from patients with erythrodermic inflammatory dermatoses with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of Sezary syndrome versus erythrodermic inflammatory dermatoses.Peer reviewe

Unsachgemäße Systemtherapie bei schwerer atopischer Dermatitis – fatale Langzeitschäden

ZusammenfassungDie Therapiemöglichkeiten der schweren atopischen Dermatitis waren bis vor Kurzem sehr begrenzt und haben sich mit der Zulassung des ersten Biologikums Dupilumab Ende 2017 bis heute deutlich verbessert. Aktuell wurden mit dem Biologikum Tralokinumab sowie den Januskinase-Inhibitoren Baricitinib und Upadacitinib weitere neue Systemtherapeutika zugelassen. Dennoch gibt es Fälle, in denen es zur Nichtberücksichtigung moderner Behandlungsmöglichkeiten kommt, wie die Falldarstellung eines 28-jährigen Patienten mit schwerwiegenden Nebenwirkungen einer Langzeitbehandlung mit systemischen Glukokortikosteroiden zeigt. Neben der umfangreichen Abklärung der Folgeschäden, erfolgten die Einleitung einer leitliniengerechten Therapie mit Dupilumab sowie eine interdisziplinäre Zusammenarbeit mit Endokrinologen, Ophthalmologen, Osteologen und Ernährungsmedizinern.</jats:p